Gastric bypass surgical procedures whose original intended result was to cause weight loss by virtue of a major decrease in nutrient absorption, in addition to a significant degree of success toward that end, have also resulted in the amelioration or elimination of Type 2 diabetes mellitus in 70-80% of post-operative patients. The prevalence and the extremely quick time course of this effect in reducing diabetes was not generally anticipated, nor can it be satisfactorily explained by weight loss alone.
It has been hypothesized (Rubino and Gagner, “Potential of surgery for curing type 2 diabetes mellitus”, Annals of Surgery (2002) 236 (5), 554-559, Rubino and Marescaux, “Effect of duodenal-jejunal exclusion in a non-obese animal model of type 2 diabetes: a new perspective for an old disease” Annals of Surgery (2004) 240(2): 389-391) that the removal or functional compromise of endocrine and neural cells within the epithelium of the intestinal tract, the small bowel in particular, which normally respond to the passage of nutrient flow were at least partially responsible for the decrease in diabetes symptoms in these treated patients. Various hormones secreted by endocrine cells in the duodenum and jejunum are collectively known as incretins, and include gastroinhibitory peptide (GIP), glucagon-like peptide (GLP-1), and insulin-like growth factor (IGF-1). The passage or presence of nutrients in the intestine stimulate the release of these hormones which have a broadly stimulatory effect on insulin secretion by the pancreas, and on enhancing the effectiveness of insulin on its targets. This relationship makes sense in that insulin helps the body to move glucose and amino acids from the blood stream into tissues, and thus the incretins prepare the body to receive nutrients that are sensed within the intestine even before the nutrients move into the bloodstream. In the pathogenesis of diabetes, however, there is an excessive amount of insulin secreted, and in response the cells responsive to insulin become overly stimulated and compensate by becoming insulin resistant. The patient with type 2 diabetes thus has a surfeit of insulin, but physiologically acts as if there is an insulin deficit. Accordingly, insulin levels and blood glucose levels are high. Whether the initial disturbance is diabetes or an over consumption of calories independent of diabetes, the end result is similar, and most obese patients are have type 2 (non-insulin-dependent) diabetes mellitus.
Other factors may be involved in the striking anti-diabetic response to bariatric surgery, such as an increase in the levels of anti-incretin factors, which would favor the effectiveness of insulin action. Additionally, the stomach wall itself is a source of hormones such as cholecystokinin (CCK), gastrin, and ghrelin, all of which play various roles in the handling of nutrients, the activity of other hormones, particularly pancreatic hormones, and on the sensation of satiety, which has further neural and behavioral consequences. Additionally, the intestine is well innervated with chemically sensitive receptors that respond to the nutrients in the stomach and intestine, and mechanically sensitive cells that respond to the volume of material in the gut and the state of smooth muscle in the intestinal wall.
Bariatric by-pass surgeries have thus been remarkably successful in decreasing nutrient intake and nutrient absorption, and have had further beneficial effects that enhance their anti-obesity effect with what appears to be a related but separable anti-diabetic effect. Surgeries such as these, however are extremely costly for the health care system as whole, and carry substantial risk of surgical morbidity and mortality. Even advocates of the use of bariatric surgery for obesity are cautious in recommending surgery as a treatment for diabetes. Clearly, however, diabetes is a major and growing public health problem, and interventions that would bring any of the remarkable effectiveness of bypass surgery but with decreased associated costs and risks would be a highly desirable addition to the currently available treatments for metabolic conditions and diseases such as morbid obesity, metabolic syndrome, and type 2 diabetes.